PET Imaging in Chronic Traumatic Encephalopathy
| Status: | Completed |
|---|---|
| Conditions: | Neurology, Neurology, Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 8/10/2017 |
| Start Date: | August 1, 2014 |
| End Date: | October 12, 2016 |
Background:
- Chronic traumatic encephalopathy (CTE) is a brain disease caused in part by head injury.
The brain changes from CTE can only be seen at autopsy. Researchers want to test a new brain
scan to help diagnose CTE in living patients.
Objective:
- To determine if a new type of brain scan can detect changes that occur in chronic traumatic
encephalopathy.
Eligibility:
- Adults age 18 60 with previous head injury or participation in certain sports.
Design:
- Participants will be screened with:
- Physical exam
- Blood and urine tests
- Tests of thinking, mood, and memory
- 30-minute magnetic resonance imaging (MRI) brain scan. A magnetic field and radio waves
take pictures of the brain. Participants will lie on a table that slides into a metal
cylinder. They will get earplugs for the loud knocking sounds.
- Visit 1: Participants will have a 70-minute PET scan of the brain with a small amount of
a radioactive chemical. That will be injected through an intravenous tube (catheter) in
each arm. A catheter will also be put into an artery at the wrist or elbow.
- Participants will lie on a bed that slides in and out of a donut-shaped scanner. A
plastic mask may be molded to their face and head. Vital signs and heart activity will
be checked before and during the scan.
- Blood and urine will be taken before and after the scan.
- Participants will be checked on by phone the next day.
- Visit 2: Participants will repeat Visit 1 with a different chemical and no artery
catheter.
- Visit 3: Participants may have a spinal tap. Some fluid will be removed by needle
between the bones in the back.
- Chronic traumatic encephalopathy (CTE) is a brain disease caused in part by head injury.
The brain changes from CTE can only be seen at autopsy. Researchers want to test a new brain
scan to help diagnose CTE in living patients.
Objective:
- To determine if a new type of brain scan can detect changes that occur in chronic traumatic
encephalopathy.
Eligibility:
- Adults age 18 60 with previous head injury or participation in certain sports.
Design:
- Participants will be screened with:
- Physical exam
- Blood and urine tests
- Tests of thinking, mood, and memory
- 30-minute magnetic resonance imaging (MRI) brain scan. A magnetic field and radio waves
take pictures of the brain. Participants will lie on a table that slides into a metal
cylinder. They will get earplugs for the loud knocking sounds.
- Visit 1: Participants will have a 70-minute PET scan of the brain with a small amount of
a radioactive chemical. That will be injected through an intravenous tube (catheter) in
each arm. A catheter will also be put into an artery at the wrist or elbow.
- Participants will lie on a bed that slides in and out of a donut-shaped scanner. A
plastic mask may be molded to their face and head. Vital signs and heart activity will
be checked before and during the scan.
- Blood and urine will be taken before and after the scan.
- Participants will be checked on by phone the next day.
- Visit 2: Participants will repeat Visit 1 with a different chemical and no artery
catheter.
- Visit 3: Participants may have a spinal tap. Some fluid will be removed by needle
between the bones in the back.
Objective: To determine if the PET radioligand [11C]PBB3 can detect aggregates of tau protein
in the brains of patients with history of traumatic brain injury (TBI) and suspected chronic
traumatic encephalopathy (CTE).
Study population: The proposed study will include 40 subjects. Twenty will be patients with
history of TBI and suspected CTE and 20 will be healthy cognitively normal volunteers without
history of TBI.
Design: Subjects will undergo medical screening and have brain MRI and neuropsychological
testing performed. Subjects will undergo one brain PET scan with [11C]PBB3 to detect
aggregates of tau protein. Subjects will also have one brain PET scan with [11C]Pittsburgh
compound B (PIB) to detect amyloid plaques. Subjects will be asked to have a lumbar puncture
to measure CSF tau concentrations.
Outcome measures: The primary outcome measure will be the amount of [11C]PBB3 binding in the
brain. We will quantify the radioligand s brain uptake, washout, plasma clearance, and
distribution volume using compartmental modeling. Distribution volume of [11C]PBB3 is
proportional to the density of insoluble paired helical filaments of tau and is equal to the
ratio at equilibrium of uptake in brain to the concentration of parent radiotracer in plasma.
As an exploratory measure, we will determine if there is a relationship between [11C]PBB3
binding in brain and gray matter loss on MRI. We will also measure the amount of [11C]PIB
binding in the brain using the Logan reference tissue method with cerebellum as reference.
in the brains of patients with history of traumatic brain injury (TBI) and suspected chronic
traumatic encephalopathy (CTE).
Study population: The proposed study will include 40 subjects. Twenty will be patients with
history of TBI and suspected CTE and 20 will be healthy cognitively normal volunteers without
history of TBI.
Design: Subjects will undergo medical screening and have brain MRI and neuropsychological
testing performed. Subjects will undergo one brain PET scan with [11C]PBB3 to detect
aggregates of tau protein. Subjects will also have one brain PET scan with [11C]Pittsburgh
compound B (PIB) to detect amyloid plaques. Subjects will be asked to have a lumbar puncture
to measure CSF tau concentrations.
Outcome measures: The primary outcome measure will be the amount of [11C]PBB3 binding in the
brain. We will quantify the radioligand s brain uptake, washout, plasma clearance, and
distribution volume using compartmental modeling. Distribution volume of [11C]PBB3 is
proportional to the density of insoluble paired helical filaments of tau and is equal to the
ratio at equilibrium of uptake in brain to the concentration of parent radiotracer in plasma.
As an exploratory measure, we will determine if there is a relationship between [11C]PBB3
binding in brain and gray matter loss on MRI. We will also measure the amount of [11C]PIB
binding in the brain using the Logan reference tissue method with cerebellum as reference.
- INCLUSION CRITERIA:
- For patients:
- History of head injury resulting from past or current participation in one or
more contact sports (hockey, football, or boxing). Patients may have history of
structural brain injury (i.e., injury accompanying abnormality on MRI or CT
scan), concussion without structural injury (mild TBI), or repetitive
sub-concussive injury.
- Meets DMS-V criteria for Major Neurocognitive Disorder or Mild Neurocognitive
Disorder
- Age 18 to 60 years.
- Ambulatory.
- Patients unable to provide informed consent must have a surrogate decision maker.
- For healthy controls:
- Healthy without past or present history of brain disease.
- Age 18 to 60 years.
- Able to provide informed consent.
EXCLUSION CRITERIA:
- Past or present history of a brain disorder other than TBI.
- For patients: Subjects with abnormal brain imaging findings that suggest a diagnosis
other than TBI or a second lesion such as brain tumor in addition to the changes
consistent with TBI.
- For controls: past or present history of either a single concussion or more severe
TBI, or of repetitive sub-concussive injury due to contact sport participation.
- Serious medical conditions, which make study procedures of the current study unsafe.
Such serious medical conditions include uncontrolled epilepsy and multiple serious
injuries. The Principal Investigator of this protocol will determine whether the
subject needs to be excluded.
- The DSM-V criteria for Major Neurocognitive Disorder are as follows:
--Evidence of significant cognitive decline from a previous level of performance in
one or more cognitive domains (complex attention, executive function, learning and
memory, perceptual-motor, or social cognition) based on:
- Concern of the individual, a knowledgeable informant, of the clinician that there
has been a significant decline in cognitive function.
- A substantial impairment in cognitive performance, preferably documented by
standardized neuropsychological testing, or, in its absence, another qualified
clinical assessment.
- The cognitive deficits interfere with independence in everyday activities (i.e. at a
minimum, requiring assistance with complex instrumental activities of daily living
such as paying bills or managing medications)
- The cognitive deficits do not occur exclusively in the context of delirium.
- The cognitive disorder is not better explained by another mental disorder (e.g. major
depressive disorder, schizophrenia).
- Criteria for Mild Neurocognitive Disorder are as follows:
- There is evidence of modest cognitive decline from a previous level of
performance in one or more of the domains outlined above based on:
- Concern of the individual, a knowledgeable informant, or the clinician.
- Decline in neurocognitive performance, preferably documented by standardized
neuropsychological testing, or, in its absence, another qualified clinical
assessment.
- The cognitive deficits are insufficient to interfere with independence (eg,
instrumental activities of daily living, like more complex tasks such as paying
bills or managing medications,
are preserved), but greater effort, compensatory strategies, or accommodation may be
required to maintain independence.
- The cognitive deficits do not occur exclusively in the context of a delirium.
- The cognitive deficits are not primarily attributable to another mental disorder (eg,
major depressive disorder, schizophrenia).
There are no restrictions on medications. Since disease modifying therapy for tauopathies
(including CTE and Alzheimer s disease) do not currently exist, no currently available
medications, either prescribed or over-the-counter, are expected to confound the results of
this study. Anti-inflammatory medications, including NSAIDs, are not expected to
significantly reduce tau aggregation in CTE patients, based on the failure of these
medications to prevent disease progression in Alzheimer s disease.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
Click here to add this to my saved trials
